Development and validation of long-acting recombinant human TSH using SAFA technology

Area of Science:

• Endocrinology
• Biotechnology
• Pharmacology

Background:

• Recombinant human thyroid-stimulating hormone (rhTSH) has a short half-life, requiring frequent administration.
• Developing a long-acting rhTSH formulation is crucial for improved therapeutic efficacy.

Purpose of the Study:

• To develop and validate a long-acting rhTSH using anti-serum albumin Fab-associated (SAFA) technology.
• To assess the biological activity, pharmacokinetics, and pharmacodynamics of SAFA-TSH.

Main Methods:

• SAFA-TSH produced via Chinese hamster ovary expression system.
• In vitro assays using Nthy-ori 3-1 cells overexpressing TSHR to measure cAMP production.
• Pharmacokinetic and pharmacodynamic studies in mouse and rat models, including TSH-suppressed models.

Main Results:

• SAFA-TSH demonstrated dose-dependent cAMP production, though less potent than Thyrogen at equivalent concentrations.
• SAFA-TSH required six times the dose of Thyrogen for similar cAMP induction.
• SAFA-TSH exhibited significantly prolonged elevation of thyroxine (T4) and free T4 levels compared to Thyrogen.

Conclusions:

• SAFA technology successfully created a bioavailable, long-acting rhTSH.
• SAFA-TSH shows potential as an improved therapeutic option for thyroid cancer treatment.
• Further clinical development of SAFA-TSH is warranted.